J. Pool (Jan)http://repub.eur.nl/ppl/2317/
List of Publicationsenhttp://repub.eur.nl/eur_signature.pnghttp://repub.eur.nl/
RePub, Erasmus University RepositoryThe Human Minor Histocompatibility Antigen1 Is a RhoGAPhttp://repub.eur.nl/pub/41606/
Mon, 23 Sep 2013 00:00:01 GMT<div>B.J. de Kreuk</div><div>A. Schaefer</div><div>E.C. Anthony</div><div>S. Tol</div><div>M. Fernandez-Borja</div><div>D. Geerts</div><div>J. Pool</div><div>L. Hambach</div><div>E. Goulmy</div><div>P.L. Hordijk</div>
The human minor Histocompatibility Antigen HMHA-1 is a major target of immune responses after allogeneic stem cell transplantation applied for the treatment of leukemia and solid tumors. The restriction of its expression to hematopoietic cells and many solid tumors raised questions regarding its cellular functions. Sequence analysis of the HMHA-1 encoding HMHA1 protein revealed the presence of a possible C-terminal RhoGTPase Activating Protein (GAP) domain and an N-terminal BAR domain. Rho-family GTPases, including Rac1, Cdc42, and RhoA are key regulators of the actin cytoskeleton and control cell spreading and migration. RhoGTPase activity is under tight control as aberrant signaling can lead to pathology, including inflammation and cancer. Whereas Guanine nucleotide Exchange Factors (GEFs) mediate the exchange of GDP for GTP resulting in RhoGTPase activation, GAPs catalyze the low intrinsic GTPase activity of active RhoGTPases, resulting in inactivation. Here we identify the HMHA1 protein as a novel RhoGAP. We show that HMHA1 constructs, lacking the N-terminal region, negatively regulate the actin cytoskeleton as well as cell spreading. Furthermore, we show that HMHA1 regulates RhoGTPase activity in vitro and in vivo. Finally, we demonstrate that the HMHA1 N-terminal BAR domain is auto-inhibitory as HMHA1 mutants lacking this region, but not full-length HMHA1, showed GAP activity towards RhoGTPases. In conclusion, this study shows that HMHA1 acts as a RhoGAP to regulate GTPase activity, cytoskeletal remodeling and cell spreading, which are crucial functions in normal hematopoietic and cancer cells. Risk factors for exercise-related acute cardiac events. A case-control studyhttp://repub.eur.nl/pub/32548/
Tue, 01 Sep 2009 00:00:01 GMT<div>W.M. van Teeffelen</div><div>M.F. de Beus</div><div>A. Mosterd</div><div>M.L. Bots</div><div>J. Pool</div><div>P.A. Doevendans</div><div>D.E. Grobbee</div>
Background: In spite of the benefits of physical activity, exercise may provoke acute cardiac events in susceptible individuals. Understanding risk factors of exercise-related acute cardiac events may identify opportunities for prevention. Methods: A case-control study was conducted to examine determinants of acute cardiac events in athletes. The cases were athletes who suffered an acute cardiac event during or shortly after vigorous exercise. Athletes who visited a hospital because of a minor sports injury were selected as controls. Information on cardiovascular disease, family history of cardiovascular disease, cardiovascular symptoms and other potential risk factors was collected through questionnaires. Results: 57 cases (mean age 41.8 years, range 11-73) and 57 controls (mean age 40.9 years, range 13-68) were included in the study. Athletes with a history of cardiovascular disease were at a markedly increased risk for cardiac events during exercise (OR=32; 95% CI 7.4 to 143). Smoking (OR 5.9; 95% CI 1.9 to 18), fatigue (OR=12; 95% CI 1.2 to 118) and flu-like symptoms (OR 13; 95% CI 1.4 to 131) in the month preceding the event were related to acute cardiac events in athletes. Conclusions: Prior cardiovascular disease, smoking, and a recent episode of fatigue or flu-like symptoms are associated with an increased risk of exercise-related acute cardiac events. Athletes and physicians should pay careful attention when these factors exist or occur.The diallelic locus encoding the minor histocompatibility antigen HA-1 is evolutionarily conservedhttp://repub.eur.nl/pub/62325/
Sat, 01 Jul 2006 00:00:01 GMT<div>B. Wieles</div><div>J. Pool</div><div>M. Wilke</div><div>M. Weber</div><div>H.-J. Kolb</div><div>R.E. Bontrop</div><div>E. Goulmy</div>
The polymorphic minor histocompatibility antigen HA-1 induces powerful T-cell alloreactivities with important consequences for graft-vs-tumor activity and development of graft-vs-host disease in patients after human leukocyte antigen-matched stem-cell transplantation (SCT). In view of possible translational animal studies, we analyzed the evolutionary conservation of the diallelic HA-1 locus in four mammalian species. Our results show that rodents do not encode the HA-1H allele, neither show polymorphism in this position on the HA-1 gene. Contrariwise, the HA-1H allele is present in non-human primate species and dogs. Interestingly, both the HA-1H T-cell epitope and its non-immunogenic counterpart HA-1R are present in the latter species. Thus, the HA-1 allelic polymorphism is conserved in evolution in primates and dogs.Well shaped ST segment and risk of cardiovascular mortalityhttp://repub.eur.nl/pub/5437/
Sat, 08 Feb 1992 00:00:01 GMT<div>E.G. Schouten</div><div>J. Pool</div><div>M.L. Simoons</div><div>J.M. Dekker</div>
OBJECTIVE--To investigate the prognostic value of frequently occurring slight variations in the ST segment for cardiovascular mortality in healthy subjects. DESIGN--Follow up study of mortality in relation to variations in ST segment level in a cohort over the 28 years from 1953 to 1981. A case-cohort sampling design was applied to limit the number of electrocardiograms that had to be coded by hand. SETTING--General health examination carried out in 1953 of civil servants in Amsterdam and assessment of subsequent mortality. SUBJECTS--Apparently healthy civil servants aged 40 to 65 years: 1583 men and 1508 women. MAIN OUTCOME MEASURES--Relative risk of variations in ST segment level for mortality from all causes, cardiovascular disease, and coronary heart disease. RESULTS--In men the multivariate relative risks of 15 year mortality from cardiovascular disease and coronary heart disease of slight ST elevation at 80 ms past the J point (compared with isoelectric ST segment) were 0.5 (95% confidence interval 0.3 to 0.9) and 0.4 (0.2 to 0.8), respectively. As expected, ST segment depression (greater than 0.25 mm) was associated with increased risk: 1.9 (1.1 to 3.0) and 2.2 (1.2 to 3.9), respectively. In women associations were weaker. The full 28 year period showed a similar pattern of somewhat weaker associations for men; among women, however, no predictive value was apparent. CONCLUSION--These results are empirical evidence for the intuitive opinion among doctors that a curved, upward sloping ST segment, resulting in slight ST elevation at 80 ms, indicates low risk compared with the isoelectric flat, stretched ST segment.Het plotse onverwachte eindehttp://repub.eur.nl/pub/7434/
Fri, 13 Sep 1991 00:00:01 GMT<div>J. Pool</div>
Psychic effects of physical training and relaxation therapy after myocardial infarctionhttp://repub.eur.nl/pub/58953/
Mon, 01 Jan 1990 00:00:01 GMT<div>J. van Dixhoorn</div><div>H.J. Duivenvoorden</div><div>J. Pool</div><div>F. Verhage</div>
Clinical value of exercise testing in elderly patientshttp://repub.eur.nl/pub/5308/
Sun, 01 Jan 1984 00:00:01 GMT<div>J. Pool</div><div>M.G. Scheffer</div><div>M.L. Simoons</div><div>N. Patijn</div>
Between 1978 and 1983, 1391 exercise tests were performed by 1083 males and 308 females over 64 years of age. This represents 17% of the total number of 8213 exercise tests. A history of myocardial infarction was present in 53% of the males and 30% of the females, while 12% of patients had previous heart surgery. Exercise was performed on a bicycle ergometer with stepwise workload increments of 10 or 20 W min-1. In 10% of patients the physician stopped the test because of serious arrhythmias or abnormal blood pressure response. The test was terminated because of fatigue (40%), angina (12%), dyspnea (18%) or tired legs and claudicatio (18%). Peak workload averaged 115 W in males and 85 W in females, which corresponds to 120% of the predicted normal values. Heart rate increased on average to 130 beats min-1 and systolic blood pressure increased to 180 mmHg. ECG changes compatible with myocardial ischaemia were observed in 42% of patients. Although elderly patients constitute a small fraction of the population referred for exercise testing, these findings indicate that the clinical value of the test when performed is similar to that in younger patients. The observation that most patients achieved higher than 'normal' maximum workloads may be due to unreliability of the reference values.Ischemic polarcardiographic changes induced by exercise; a new criterionhttp://repub.eur.nl/pub/5210/
Mon, 01 Jan 1973 00:00:01 GMT<div>G.E. Dower</div><div>R.A. Bruce</div><div>J. Pool</div><div>M.L. Simoons</div><div>M.W. Niederberger</div><div>L.J. Meilink</div>